Caudal epidural anesthesia during intracavitary brachytherapy for cervical cancer

It has been suggested that pain control during intracavitary brachytherapy for cervical cancer is insufficient in most hospitals in Japan. Our hospital began using caudal epidural anesthesia during high-dose-rate (HDR) intracavitary brachytherapy in 2011. The purpose of the present study was to retrospectively investigate the effects of caudal epidural anesthesia during HDR intracavitary brachytherapy for cervical cancer patients. Caudal epidural anesthesia for 34 cervical cancer patients was performed during HDR intracavitary brachytherapy between October 2011 and August 2013. We used the patients'' self-reported Numeric Rating Scale (NRS) score at the first session of HDR intracavitary brachytherapy as a subjective evaluation of pain. We compared NRS scores of the patients with anesthesia with those of 30 patients who underwent HDR intracavitary brachytherapy without sacral epidural anesthesia at our hospital between May 2010 and August 2011. Caudal epidural anesthesia succeeded in 33 patients (97%), and the NRS score was recorded in 30 patients. The mean NRS score of the anesthesia group was 5.17 ± 2.97, significantly lower than that of the control group''s 6.80 ± 2.59 (P = 0.035). The caudal epidural block resulted in no side-effects. Caudal epidural anesthesia is an effective and safe anesthesia option during HDR intracavitary brachytherapy for cervical cancer.     

Inverse planning for combination of intracavitary and interstitial brachytherapy for locally advanced cervical cancer

The main purpose of this study was to compare three different treatment plans for locally advanced cervical cancer: (i) the inverse-planning simulated annealing (IPSA) plan for combination brachytherapy (BT) of interstitial and intracavitary brachytherapy, (ii) manual optimization based on the Manchester system for combination-BT, and (iii) the conventional Manchester system using only tandem and ovoids. This was a retrospective study of 25 consecutive implants. The high-risk clinical target volume (HR-CTV) and organs at risk were defined according to the GEC-ESTRO Working Group definitions. A dose of 6 Gy was prescribed. The uniform cost function for dose constraints was applied to all IPSA-generated plans. The coverage of the HR-CTV by IPSA for combination-BT was equivalent to that of manual optimization, and was better than that of the Manchester system using only tandem and ovoids. The mean V₁₀₀ achieved by IPSA for combination-BT, manual optimization and Manchester was 96 ± 3.7%, 95 ± 5.5% and 80 ± 13.4%, respectively. The mean D₁₀₀ was 483 ± 80, 487 ± 97 and 335 ± 119 cGy, respectively. The mean D₉₀ was 677 ± 61, 681 ± 88 and 513 ± 150 cGy, respectively. IPSA resulted in significant reductions of the doses to the rectum (IPSA D_2cm³: 408 ± 71 cGy vs manual optimization D_2cm³: 485 ± 105 cGy; P = 0.03) and the bladder (IPSA D_2cm³: 452 ± 60 cGy vs manual optimization D_2cm³: 583 ± 113 cGy; P < 0.0001). In conclusion, combination-BT achieved better tumor coverage, and plans using IPSA provided significant sparing of normal tissues without compromising CTV coverage.     

Different effects of bladder distention on point A-based and 3D-conformal intracavitary brachytherapy planning for cervical cancer

This study sought to evaluate the differential effects of bladder distention on point A-based (AICBT) and three-dimensional conformal intracavitary brachytherapy (3D-ICBT) planning for cervical cancer. Two sets of CT scans were obtained for ten patients to evaluate the effect of bladder distention. After the first CT scan, with an empty bladder, a second set of CT scans was obtained with the bladder filled. The clinical target volume (CTV), bladder, rectum, and small bowel were delineated on each image set. The AICBT and 3D-ICBT plans were generated, and we compared the different planning techniques with respect to the dose characteristics of CTV and organs at risk. As a result of bladder distention, the mean dose (D₅₀) was decreased significantly and geometrical variations were observed in the bladder and small bowel, with acceptable minor changes in the CTV and rectum. The average D_{2 cm³}and D_{1 cm³}showed a significant change in the bladder and small bowel with AICBT; however, no change was detected with the 3D-ICBT planning. No significant dose change in the CTV or rectum was observed with either the AICBT or the 3D-ICBT plan. The effect of bladder distention on dosimetrical change in 3D-ICBT planning appears to be minimal, in comparison with AICBT planning.     

Comparison of predictive performance for toxicity by accumulative dose of DVH parameter addition and DIR addition for cervical cancer patients

We compared predictive performance between dose volume histogram (DVH) parameter addition and deformable image registration (DIR) addition for gastrointestinal (GI) toxicity in cervical cancer patients. A total of 59 patients receiving brachytherapy and external beam radiotherapy were analyzed retrospectively. The accumulative dose was calculated by three methods: conventional DVH parameter addition, full DIR addition and partial DIR addition. , and (minimum doses to the most exposed 2 cm³, 1cm³ and 0.1 cm³ of tissue, respectively) of the rectum and sigmoid were calculated by each method. V50, V60 and V70 Gy (volume irradiated over 50, 60 and 70 Gy, respectively) were calculated in full DIR addition. The DVH parameters were compared between toxicity (≥grade1) and non-toxicity groups. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves were compared to evaluate the predictive performance of each method. The differences between toxicity and non-toxicity groups in were 0.2, 5.7 and 3.1 Gy for the DVH parameter addition, full DIR addition and partial DIR addition, respectively. The AUCs of were 0.51, 0.67 and 0.57 for DVH parameter addition, full DIR addition and partial DIR addition, respectively. In full DIR addition, the difference in dose between toxicity and non-toxicity was the largest and AUC was the highest. AUCs of V50, V60 and V70 Gy were 0.51, 0.63 and 0.62, respectively, and V60 and V70 were high values close to the value of of the full DIR addition. Our results suggested that the full DIR addition may have the potential to predict toxicity more accurately than the conventional DVH parameter addition, and that it could be more effective to accumulate to all pelvic irradiation by DIR.     

Small dose of oral gastrografin for computed tomography-based image-guided brachytherapy in patients with uterine cervical cancer

Oral administration of a water-soluble iodine contrast agent (gastrografin) was reported to assist in the appropriate contouring of the small intestine on computed tomography (CT)-based radiotherapy (RT) planning. The efficacy and optimal dose of gastrografin in CT-based image-guided brachytherapy (IGBT) for cervical cancer remain unknown. This study aimed to investigate the efficacy of pretreatment oral administration of gastrografin at a small dose of 50 ml in CT-based IGBT for cervical cancer. A total of 422 sessions in 137 patients who underwent CT-based IGBT with 50 ml of oral gastrografin (concentration, 3% or 4%) were analyzed. Preparation of gastrografin was judged as effective when the small intestine was contrast-enhanced at the area where the small intestine was in contact with the uterus/adnexa. About 287 out of 422 sessions (68%) were judged as effective with gastrografin preparation. The 135 ineffective sessions were considered as follows: (i) the contrast enhancement of the small intestine was not confirmed (n = 36), (ii) the small intestine was not in contact with the uterus/adnexa despite the confirmation of the contrast enhancement of the small intestine (n = 34), and (iii) gastrografin was absent in the small intestine at the area in contact with the uterus/adnexa, even when gastrografin was observed in the small intestine at the area not in contact with the uterus/adnexa (n = 65). In conclusion, pretreatment oral administration of a small dose gastrografin achieved moderate efficacy for accurate contouring of the small intestine close to the uterus/adnexa in CT-based IGBT for cervical cancer.     

Clinical results of external beam radiotherapy alone with a concomitant boost program or with conventional fractionation for cervical cancer patients who did not receive intracavitary brachytherapy

A combination of external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) is well established as the standard radical radiotherapy (RT) for cervical cancer. However, it is sometimes necessary to perform EBRT alone for patients where ICBT is not feasible. For these patients, we initiated EBRT alone with three-dimensional conformal radiotherapy (3DCRT). The purpose of this study is to evaluate the results of EBRT alone without ICBT for patients with cervical cancer. Sixteen patients were treated with EBRT alone between 2002 and 2009. There were three stage IIB, six stage IIIB and seven patients with stage IVA disease. A total of 10 patients were treated with a median dose of 66 Gy with a median overall treatment time (OTT) of 40 days delivered by a concomitant boost (CCB), and a median dose of 60 Gy with a median OTT of 47 days was administered for six patients by conventional fractionation (CF). The 3-year overall survival (OAS) and local control (LC) rates were 43.8% and 75.0%, respectively. The 3-year LC rate was 90.0% for the CCB group, 50.0% for the CF group (P = 0.0692); 100% for OTT ≤42 days, 42.9% for OTT ≥43 days (P = 0.0095). No severe acute and late adverse effects were encountered for any of the patients. These outcomes suggest that EBRT with a CCB program may be a promising radical treatment for cervical cancer that provides better LC with minimal complications, especially in cases where ICBT cannot be performed.     

直肠癌同步调强放疗不同射野角度对小肠和膀胱受照剂量的影响研究

目的:研究俯卧位下不同射野角度的直肠癌同步整合加量静态调强放疗计划中小肠和膀胱受照剂量的差异。方法:选取10例行同步整合加量静态调强放疗直肠癌患者,均按照相同的处方剂量要求在Pinnacle计划系统中进行计划优化设计,每位患者均设计3组计划:A计划(前5野)、B计划(5野均分)、C计划(7野均分),比较靶区均匀性指数(homogeneity index,HI)、适形度指数(conformity index,CI)、靶区剂量、总机器跳数及小肠、膀胱、股骨头和外阴受照体积。采用SPSS 19.0进行统计学分析。结果:3组计划的靶区剂量分布及膀胱和外阴危及器官体积限量均符合临床要求且没有显著性差异。但A计划小肠V15明显低于另两组,A计划与C计划间差异显著(P<0.05)。结论:直肠癌放疗应综合考虑肿瘤的大小和所在位置,在俯卧位下选择前5野照射不仅能满足临床处方剂量,还可降低急性放射性肠炎的发生率,在仅开展静态调强放疗的单位具有较好的实用性。     

Clinical results and toxicity for short-course preoperative radiotherapy and total mesorectal excision in rectal cancer patients

Short-course preoperative radiotherapy (SCPRT) is an alternative method to chemoirradiation for patients with Stage II and III rectal cancer when no downsizing is needed, but there is still widespread reluctance to use this method because of fear of side effects from high-fraction doses. This paper reports on a single institution patient cohort of operated rectal cancer patients after SCPRT, evaluated for chronic adverse effects, local control, progression-free survival and overall survival. Altogether, 257 patients were treated with SCPRT and surgery including total mesorectal excision (92% total mesorectal excision = TME) between 2002 and 2009. Local control and survival were analyzed. Chronic adverse effects for 154 patients without local relapse were evaluated according to the NCI–CTCAE version 4.0 classification, with a median follow-up of 48 months. We found a 5-year disease-free survival (DFS) and overall survival (OS) of 71%. The 5-year estimated local control (LC) rate was 94%. A positive resection margin was found in 4% of the patients and was significantly correlated with decreased DFS, OS and LC. Chronic adverse effects were reported by 58% of the patients, of which 10% were Grade 3 toxicities. The most frequent Grade 2 toxicity was stool incontinence (13%). Sexual dysfunction was found in 36% of the patients (31% Grade 1 or 2, and only 5% Grade 3). SCPRT combined with TME produced excellent LC rates together with a low rate of high-grade chronic adverse effects.     

Interfractional change of high-risk CTV D90 during image-guided brachytherapy for uterine cervical cancer

The purpose of this study was to evaluate interfractional changes of the minimum dose delivered to 90% of the high-risk clinical target volume (HR-CTV D90) and D2cc of the bladder and rectum during brachytherapy for uterine cervical cancer patients. A total of 52 patients received external beam radiotherapy and high-dose-rate intracavitary brachytherapy (ICBT). For each of four ICBT applications, a pelvic CT scan was performed and the HR-CTV was delineated. Retrospectively, these patients were divided into two groups: (i) the standard dose group with 6 Gy to point A in each ICBT, and (ii) the adaptive dose group with a modified dose to point A to cover the HR-CTV with the 6-Gy isodose line as much as possible. The HR-CTV D90 was assessed in every session, and analyzed as interfractional changes. In the standard dose group, the interfractional changes of the HR-CTV D90 showed a linear increase from the first to the third of the four ICBT (average 6.1, 6.6, 7.0 and 7.1 Gy, respectively). In contrast, those of the adaptive dose group remained almost constant (average 7.2, 7.2, 7.3 and 7.4 Gy, respectively). Especially, in the case of a large HR-CTV volume (≥35 cm³) at first ICBT, the total HR-CTV D90 of the adaptive dose group with brachytherapy was significantly higher than that of the standard dose group. There were no significant differences in total D2cc in bladder and rectum between the two groups. Image-guided adaptive brachytherapy based on interfractional tumor volume change improves the dose to the HR-CTV while keeping rectal and bladder doses within acceptable levels.     

External beam boost irradiation for clinically positive pelvic nodes in patients with uterine cervical cancer

The purpose of this study was to retrospectively analyze the treatment results of boost external beam radiotherapy (EBRT) to clinically positive pelvic nodes in patients with uterine cervical cancer. The study population comprised 174 patients with FIGO stages 1B1–4A cervical cancer who were treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients with positive para-aortic or common iliac nodes (≥10 mm in the shortest diameter, as evaluated by CT/MRI) were ineligible for the study. Fifty-seven patients (33%) had clinically positive pelvic nodes. The median maximum diameter of the nodes was 15 mm (range, 10–60 mm) and the median number of positive lymph nodes was two (range, one to four). Fifty-two of 57 patients (91%) with positive nodes were treated with boost EBRT (6–10 Gy in three to five fractions). The median prescribed dose of EBRT for nodes was 56 Gy. The median follow-up time for all patients was 66 months (range, 3–142 months). The 5-year overall survival rate, disease-free survival rate and pelvic control rate for patients with positive and negative nodes were 73% and 92% (P = 0.001), 58% and 84% (P < 0.001), and 83% and 92% (P = 0.082), respectively. Five of 57 node-positive patients (9%) developed pelvic node recurrences. All five patients with nodal failure had concomitant cervical failure and/or distant metastases. No significant difference was observed with respect to the incidence or severity of late complications by application of boost EBRT. The current retrospective study demonstrated that boost EBRT to positive pelvic nodes achieves favorable nodal control without increasing late complications.     

A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.     

Second malignancies following conventional or combined 252Cf neutron brachytherapy with external beam radiotherapy for breast cancer

We retrospectively evaluated the risk of second malignancies among 832 patients with inner or central breast cancer treated with conventional external beam schedule (CRT group), or neutron brachytherapy using Californium-252 (²⁵²Cf) sources and hypofractionated external beam radiotherapy (HRTC group), between 1987 and 1996 at the Institute of Oncology, Vilnius University. Patients were observed until the occurrences of death or development of a second malignancy, or until 31 December 2009, whichever was earlier. Median follow-up time was 10.4 years (range, 1.2–24.1 years). Risk of second primary cancers was quantified using standardized incidence ratios (SIRs). Cox proportional hazards regression models were used to estimate hazard ratios (HRs). There was a significant increase in the risk of second primary cancers compared with the general population (SIR 1.3, 95% CI 1.1–1.5). The observed number of second primary cancers was also higher than expected for breast (SIR 1.8, 95% CI 1.3–2.4) and lung cancer (SIR 3.8, 95% CI 2.0–6.7). For second breast cancer, no raised relative risk was observed during the period ≥10 or more years after radiotherapy. Compared with the CRT group, HRTC patients had a not statistically significant higher risk of breast cancer. Increased relative risks were observed specifically for age at initial diagnosis of <50 years (HR 2.9, 95% CI 1.6–5.2) and for obesity (HR 2.8, 95% CI 1.1–7.2).     

Pelvic insufficiency fracture after definitive radiotherapy for uterine cervical cancer: retrospective analysis of risk factors

The purpose of this study is to determine the incidence, clinical characteristics and risk factors of postradiation pelvic insufficiency fracture (PIF) in women with uterine cervical cancer. We reviewed the medical records of 126 patients who received definitive radiotherapy (RT) for uterine cervical cancer between 2003 and 2009 at our institution. Among them, 99 patients who underwent at least one computed tomography (CT) or magnetic resonance imaging of the pelvis during their follow-up at more than 6 months were included in this analysis. The relationship between the incidence of PIF and several patient- and treatment-related factors was analyzed. The median follow-up period was 21 months. Of the 126 patients, 33 (with a total of 50 lesions) were diagnosed with PIF. The 2-year cumulative incidence was 32%. Univariate analysis showed that age ≥70 years (P= 0.0010), postmenopausal state (P = 0.0013), and lower CT density of bone and bone marrow (P= 0.020) significantly related to PIF. In a multivariate analysis, of the 59 patients whose CT densities were evaluable, lower CT density was the only significant factor associated with PIF (P = 0.0026). In conclusion, postradiation PIFs were detected in a considerable number of patients after definitive RT for cervical cancer. Predisposing factors were older age, postmenopausal state, and decreased density of bone and bone marrow on CT.     

Dosimetric and geometric evaluation of the use of deformable image registration in adaptive intensity-modulated radiotherapy for head-and-neck cancer

The aim of this study was to carry out geometric and dosimetric evaluation of the usefulness of a deformable image registration algorithm utilized for adaptive head-and-neck intensity-modulated radiotherapy. Data consisted of seven patients, each with a planning CT (pCT), a rescanning CT (ReCT) and a cone beam CT (CBCT). The CBCT was acquired on the same day (±1 d) as the ReCT (i.e. at Fraction 17, 18, 23, 24 or 29). The ReCT served as ground truth. A deformed CT (dCT) with structures was created by deforming the pCT to the CBCT. The geometrical comparison was based on the volumes of the deformed, and the manually delineated structures on the ReCT. Likewise, the center of mass shift (CMS) and the Dice similarity coefficient were determined. The dosimetric comparison was performed by recalculating the initial treatment plan on the dCT and the ReCT. Dose–volume histogram (DVH) points and a range of conformity measures were used for the evaluation. We found a significant difference in the median volume of the dCT relative to that of the ReCT. Median CMS values were ∼2–5 mm, except for the spinal cord, where the median CMS was 8 mm. Dosimetric evaluation of target structures revealed small differences, while larger differences were observed for organs at risk. The deformed structures cannot fully replace manually delineated structures. Based on both geometrical and dosimetrical measures, there is a tendency for the dCT to overestimate the need for replanning, compared with the ReCT.     

A questionnaire-based survey on 3D image-guided brachytherapy for cervical cancer in Japan: advances and obstacles

The purpose of this study is to survey the current patterns of practice, and barriers to implementation, of 3D image-guided brachytherapy (3D-IGBT) for cervical cancer in Japan. A 30-item questionnaire was sent to 171 Japanese facilities where high-dose-rate brachytherapy devices were available in 2012. In total, 135 responses were returned for analysis. Fifty-one facilities had acquired some sort of 3D imaging modality with applicator insertion, and computed tomography (CT) and magnetic resonance imaging (MRI) were used in 51 and 3 of the facilities, respectively. For actual treatment planning, X-ray films, CT and MRI were used in 113, 20 and 2 facilities, respectively. Among 43 facilities where X-ray films and CT or MRI were acquired with an applicator, 29 still used X-ray films for actual treatment planning, mainly because of limited time and/or staffing. In a follow-up survey 2.5 years later, respondents included 38 facilities that originally used X-ray films alone but had indicated plans to adopt 3D-IGBT. Of these, 21 had indeed adopted CT imaging with applicator insertion. In conclusion, 3D-IGBT (mainly CT) was implemented in 22 facilities (16%) and will be installed in 72 (53%) facilities in the future. Limited time and staffing were major impediments.     

RAC1在宫颈癌组织中的表达及其作用

目的研究RAC1在宫颈癌组织中的表达，探讨其与宫颈癌转移的相关性。方法应用免疫组织化学SP法，检测10例正常宫颈组织、20例不典型增生宫颈组织、58例宫颈癌组织中RAC1蛋白的表达情况。分析其表达结果与临床病理特征的关系。结果（1）RAC1蛋白在正常宫颈组织中不表达，在不典型增生宫颈组织中的表达率为25．00％，在宫颈癌组织中的表达率为81．03％，在宫颈癌组织中的表达水平高于不典型增生及正常宫颈组织（P〈0．05），随着从正常宫颈组织-宫颈不典型增生组织-宫颈癌的转化，RAC1阳性表达率呈递增趋势。（2）RAC1的表达与病理分级相关（P〈0.05），与宫颈癌患者的年龄、临床分期、有无淋巴结转移则无明显相关关系（P〉0．05）。结论RAC1蛋白的表达可作为判断宫颈癌预后的指标之一。检测RAC1对了解宫颈癌生物学行为和评估预后具有一定的临床价值。